Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Abstract Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.

Síndrome de Sézary. Etiopatogenia, epidemiología, clínica, diagnóstico y pronóstico / Sézary syndrome Pathogenesis, epidemiology, clinical features, diagnosis and prognosis

El síndrome de Sézary (SS) es una rara y agresiva variante leucémica del linfoma cutáneo de células T, de pronóstico ominoso. Se caracteriza por presentar la tríada eritrodermia, linfadenopatías y linfocitos T neoplásicos circulantes. El diagnóstico está dado por la clínica, el estudio histopatológico, la citometría de flujo y el reordenamiento genético del receptor del linfocito T. En esta revisión se analizan la presentación clínica, la histopatología, el diagnóstico y el pronóstico de este síndrome. (AU)

Sézary syndrome (SS) is a rare and aggressive leukemic cutaneous T-cell lymphoma with poor prognosis. Is characterized by a triad of erythroderma, lymphadenopathy and circulating neoplastic T cells. Diagnosis is made by clinical features, histopathology, flow cytometry and T-cell receptor gene rearrangements. In this review we will analyze clinical presentation, histopathology, diagnosis and prognosis of SS. (AU)

Evaluation of the Cutaneous Lymphoma International Prognostic Index in patients with early stage mycosis fungoides

Abstract: Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. TNMB system is the staging method used in MF, and it not only guides therapeutic management, but represents the main prognostic factor. In order to improve the prognostic evaluation, the Cutaneous Lymphoma International Prognostic Index (CLIPi) was proposed. Objective: To evaluate the performance of CLIPi score for prognostic analysis in patients with early stage MF. Methods: This is a retrospective cross-sectional observational study, with exploratory analysis. The outcome variables were disease progression and related death. Results: One hundred and two patients were stratified according to CLIPi score, being the majority classified as low risk. Patients with intermediate or high risk presented disease progression more frequently than those with low risk (PR: 1.2 / p = 0.004 / 95%CI: 1.0 - 1.6). The same did not occur with the variable related death. In addition, survival rates were not consistent with risk stratification. Study Limitations: Small sample and its retrospective analysis. Conclusions: Since CLIPi score was proposed, four other studies that we could consult showed conflicting results, similar to the present study. Further studies are necessary for a recommendation of its use.

Síndrome de Sézary. Presentación de un caso / Sézary síndrome. Case presentation

RESUMEN El síndrome de Sézary constituye la fase leucémica de la micosis fungoide caracterizado por eritrodermia, adenopatías superficiales y células atípicas en sangre. Predomina en los hombres con una proporción 2/1 respecto a las mujeres, y en las edades entre los 60 y 70 años de edad. La enfermedad es de difícil tratamiento, con un pronóstico reservado por su baja supervivencia. Por ser infrecuente y su posible similitud con otras dermatosis, se presenta un caso con antecedentes de psoriasis vulgar con 5 años de evolución, que hacía aproximadamente 6 meses, se encontraba sin mejoría en brote de agudización a pesar de los tratamientos indicados (AU).

ABSTRACT Sezary syndrome is the leukemic part of the fungoid mycosis, characterized by erythroderma, surface adenopathies and atypical cells in blood. It predominates in men with a 2/1 proportion in respect to women, and in ages ranging from 60 to 70 years. It is a difficult treated disease, with a reserved prognosis because of the low survival. Due to its infrequency and possible similarity to other dermatosis, it is presented a case with antecedents of vulgar psoriasis of 5 years evolution, without improvement for around 6 months, in acute outbreak in spite of the indicated treatments (AU).

Epitheliotropic lymphoma with heart and kidney metastasis in a dog: case report / Linfoma epiteliotrópico em cão com metástase cardíaca e renal: relato de caso

A female adult dog, with a four-month history of pain and intense pruritus, which eventually resulted in sudden death, was referred for necropsy. Postmortem examination showed thoracic and abdominal serum-sanguineous exudates, multifocal infiltrative renal masses, and similar tumors in the heart. Histopathology revealed midsize infiltrative neoplastic proliferation composed of round cells, sparse cytoplasm, and large hyperchromatic nuclei. Immunohistochemistry revealed CD3+ and CD20-immunoexpression. Histopathological and immunohistochemical findings confirmed the diagnosis of epitheliotropic lymphoma with cardiac and renal metastasis.(AU)

Foi encaminhado para necropsia um cão adulto do sexo feminino, com histórico de dor e prurido intenso com evolução de quatro meses, que acabou resultando em morte súbita. O exame post mortem mostrou presença discreta de exsudato serossanguinolento em cavidades torácica e abdominal, massas renais infiltrativas multifocais e tumores semelhantes no coração. O exame histopatológico revelou proliferação neoplásica infiltrativa composta de células redondas, com citoplasma escasso, e grandes núcleos hipercromáticos. A análise imuno-histoquímica mostrou imunoexpressão CD3+e CD20. Os achados histopatológicos e imuno-histoquímico confirmaram o diagnóstico de linfoma epiteliotrópico com metástase cardíaca e renal.(AU)

Alemtuzumab in refractory Sézary syndrome

Abstract: Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by the triad of erythroderma, lymphadenopathy and circulating atypical cells. The emergence of new molecular targets has enabled the development of drugs such as alemtuzumab, an anti-CD52 monoclonal antibody, which has shown promising results in the treatment of this entity. We report the case of a 70-year-old male with refractory Sézary syndrome in whom treatment with alemtuzumab achieved an 80% skin lesion clearance with complete haematologic and radiologic response. The treatment was discontinued after 4 months due to adverse effects, with the patient showing a sustained response without disease progression after 13 months of follow-up.

Fotoféresis en el tratamiento de Síndrome de Sézary: Caso clínico / Sézary syndrome treated with extracorporeal photopheresis: Report of one case

Sézary syndrome (SS) is an unusually aggressive T- cell lymphoma characterized by the triad of erythroderma, the presence of more than 1,000 Sézary cells in peripheral blood and lymphadenopathies. It is accompanied by generalized pruritus and poor quality of life. The management of SS depends on its stage, patient comorbidities, and treatment availability. Extracorporeal photopheresis (ECP) is the first line of treatment for patients with T-cell lymphomas in stage IVA1, IVA2 or SS. This treatment comprises three phases: leukapheresis, photoactivation and subsequent reinfusion of lymphocytes. As it is an immunomodulatory therapy it does not produce generalized immunosuppression. We report a 76 year-old male with SS stage IIIb initially treated with 12 sessions of ultraviolet phototherapy without response. After 10 well-tolerated sessions of ECP, itching and skin lesions eventually disappeared.

Actualización en diagnóstico y manejo de micosis fungoide y síndrome de Sézary / Update on diagnosis and management of mycosis fungoides and Sézary's syndrome

Los linfomas cutáneos primarios consisten en una proliferación anormal de linfocitos T o B que muestran tropismo por la piel, sin evidenciarse compromiso extra cutáneo al momento del diagnóstico. Se dividen en linfomas de células T (75 por ciento-80 por ciento) y linfomas de células B (20 por ciento-25 por ciento). La micosis fungoide es una neoplasia de estirpe T y constituye el linfoma cutáneo primario más frecuente. Su presentación clínica clásica consiste en 3 etapas: parche, placa y tumor. Sin embargo, tiene múltiples variantes y un amplio diagnóstico diferencial, por lo que para su diagnóstico se requiere una estricta correlación entre la clínica y la histopatología. El síndrome de Sézary, por su parte, es considerado la variante leucémica de los linfomas cutáneos primarios y forma parte del diagnóstico diferencial de las eritrodermias. En esta revisión profundizaremos en los principales aspectos de la clínica, histopatología, criterios diagnósticos y tratamiento de la micosis fungoide y el síndrome de Sézary.

Primary cutaneous lymphomas represent an abnormal proliferation of T or B-cells with skin-homing ability, with no evidence of extra cutaneous disease at the time of diagnosis. They are divided in T-cell lymphomas (75 percent-80 percent) and B-cell lymphomas (20 percent-25percent). Mycosis fungoides (MF) is a T-cell malignancy, being the most common lymphoma. Classic MF presents 3 clinical phases: patch, plaque and tumor stage. However, it has numerous variants and a wide range of differential diagnosis, so that precise clinicopathologic correlation is necessary for make a correct diagnosis. Sézary syndrome is an aggressive leukemic primary cutaneous T-cell lymphoma variant and it is part of the spectrum of erythroderma. In this review we will analyze the main aspects about clinical presentation, histopathology, diagnosis and treatment of mycosis fungoides and Sézary syndrome.

Mycosis fungoides and Sézary syndrome: clinical, histopathological and immunohistochemical review and update / Micose fungóide e síndrome de Sézary: revisão e atualização clínica, histopatológica e imuno-histoquímica

This paper reviews the diagnostic and classificatory concepts of mycosis fungoides and Sézary syndrome in light of the latest normative publications. It describes the great variability of the clinical expression of mycosis fungoides in its early stages as well as the histopathological and immunohistochemical aspects that help with diagnosis. The diagnostic criteria required for characterizing Sézary syndrome and the staging system used for both mycosis fungoides and Sézary syndrome are described.

O artigo revisa os conceitos diagnósticos e de classificação da micose fungóide e da síndrome de Sézary a luz das publicações normativas mais recentes. Descreve a grande variabilidade de expressão clinica da micose fungóide em seus estágios iniciais assim como os aspectos histopatológicos e imuno-histoquímicos auxiliares ao diagnóstico. São descritos os critérios de diagnósticos exigidos para que se caracterize a síndrome de Sézary e o sistema de estadiamento, utilizado para ambas, micose fungóide e síndrome de Sézary.

A Comparative Histopathologic Study of Actinic Reticuloid and Mycosis Fungoides / 대한피부과학회지

BACKGROUND: Actinic reticuloid is a severe persistent photodermatitis that usually affects older men. It is characterized by extreme photosensitivity to a broad spectrum of ultraviolet radiation. Actinic reticuloid has many of the clinical and histological features of mycosis fungoides and Sezary syndrome. No Korean studies are available regarding a histopathological and immunohistochemical comparison of actinic reticuloid and mycosis fungoides. OBJECTIVE: This study was designed to evaluate the histopathological characteristics and conduct a immunophenotypic analysis to distinguish actinic reticuloid from mycosis fungoides. METHODS: We reviewed the histomorphological findings of 10 patients diagnosed with actinic reticuloid and those of 15 patients diagnosed with mycosis fungoides from 1996 to 2012 at our clinic. In addition, an immunophenotypic analysis was performed on the skin to assess the proportions of CD4+ and CD8+ T cells in all patients. RESULTS: We found a broad overlap in non-specific inflammatory histological features and more prominent histological features between the two diseases. Irregular acanthosis, vertically-streaked collagen in the papillary dermis, thickened and increased blood vessels, and an eosinophil and plasma cell infiltrate were significantly higher in patients with actinic reticuloid than in those with mycosis fungoides. Stuffed lymphocytes in dermal papillae and a psoriasiform lichenoid pattern were observed significantly more often in patients with mycosis fungoides. Solar elastosis (80%) was seen only in the actinic reticuloid cases. CD8-positive T cells were predominant in the epidermis in eight of 10 patients with actinic reticuloid. In contrast, CD4-positive T cells in the epidermis and dermis predominated in the majority of patients with mycosis fungoides (73.3%) compared with CD8-positive T cells. CONCLUSION: Histopathological findings and immunophenotypic analyses may be an important adjunct to distinguish actinic reticuloid from mycosis fungoides, but a correlation with clinicopathological findings, phototest, patch test, and photopatchtest is necessary to reliably distinguish actinic reticuloid from mycosis fungoides. Further prospective studies should be conducted on a larger number of cases regarding the differences between actinic reticuloid and mycosis fungoides.

Linfoma cutáneo de células T Revisión del tema con énfasis en la inmunopatogénesis / Cutaneous T-cell lymphoma: Review with emphasis on immunophatogenesis

Bajo el término linfoma cutáneo de células T (LCCT) se agrupa una serie de enfermedades que tienen en común la presencia de un clon maligno de células T y la afectación de la piel. La micosis fungoide (MF) es la forma más común de LCCT, seguida por el síndrome de Sèzary (SS). La causa definitiva de la MF es desconocida. El inmunofenotipo de la mayoría de los casos de MF es de células T de memoria CD3+CD4+CD45RO+CLA+CD8-. Los linfocitos T CD4+ malignos migran hasta la epidermis y se localizan alrededor de las células de Langerhans (LC). En el SS las células pierden el epidermotropismo e infiltran extensamente la dermis, la sangre y otros tejidos; estas células presentan un inmunofenotipo predominante de células T neoplásicas CD3+CD4+CD8-CD7-CD26- CD158k+CD94-. El perfil Th2 y la supresión de respuestas Th1 son dos factores críticos en la progresión de la enfermedad. Se han evaluado muy poco las alteraciones en la regulación inmune en el LCCT. Un mejor entendimiento de la función de las células T y de la inmunobiología de los LCCT permitiría mejorar el pronóstico, el tratamiento y el seguimiento de los pacientes con estas neoplasias.

The term cutaneous T-cell lymphoma (CTCL) refers to several diseases that have in common the presence of a malignant T-cell clone with involvement of the skin. Mycosis fungoides (MF) is the most common form of CTCL, followed by the Sèzary syndrome (SS). The cause of mycosis fungoides is unknown. Immunophenotype of most cases of MF is made up by memory T cells CD3+CD4+CD45RO+CLA+CD8-. Malignant T CD4+ lymphocytes migrate to the epidermis and localize around Langerhans cells. In SS, cells loose their epidermotropism and extensively infiltrate the dermis, blood and other tissues. These cells present a predominant immunophenotype of neoplasic T cells CD3+CD4+CD8-CD7-CD26-CD158k+CD94-. The Th2 profile and the supression of Th1 responses are two critical factors in the progression of the disease. Alterations in the immune regulation in CTCL have not been thoroughly evaluated. A better understanding of T-cell function and of the immunobiology of CTCL would allow to improve the prognosis, therapy and follow-up of patients with these neoplasias.

Generalized Erythroderma as a Manifestation of Sezary Syndrome / 대한피부과학회지

Sezary syndrome is a variant of cutaneous T-cell lymphoma and likely represents the leukemic phase of mycosis fungoides. Sezary syndrome is characterized by generalized erythroderma, pruritus, generalized lymphadenopathy, and circulating atypical cells with cerebriform nuclei. Histopathological features are variable, as this is a later stage in the development of mycosis fungoides. Atypical lymphocytes in the dermis and Pautrier's microabscesses may be present on a histopathological examination but up to one-third of cases may have non-specific findings. Immunological findings supporting a diagnosis of Sezary syndrome include a predominance of CD4+ lymphocytes in both skin biopsy specimens and peripheral blood. In our case, a 48-year-old male was referred for evaluation of generalized hyperpigmentation with exfoliation on his entire body. We suspected that the clinical features represented Sezary syndrome. We obtained a lymph node biopsy, immunological cell typing, and a peripheral blood smear and diagnosed Sezary syndrome.

Diagnóstico y manejo del linfoma cutáneo de células T de tipo micosis fungoides y síndrome de Sèzary / Diagnosis and treatment of cutaneous T cells lymphoma

La micosis fungoides y el síndrome de Sèzary constituyen el grupo más frecuente de linfomas cutáneos de células T; tienen un curso lento y progresivo y un impacto negativo en la calidad de vida del paciente. En los estadios iniciales, la curación es anecdótica y en los casos avanzados pueden comprometer la vida del paciente; con las opciones terapéuticas actuales se consigue disminuir la sintomatología y se logran remisiones temporales. Para los estadios tempranos se propone el uso de terapias dirigidas a la piel, como los esteroides tópicos, la fotoquimioterapia PUVA y la radioterapia localizada, y otros no disponibles en nuestro medio, como la quimioterapia tópica y el bexaroteno, mientras que, para los estadios más avanzados, se recomiendan terapias que combinan las dirigidas a la piel con tratamientos sistémicos, como el interferón alfa, el vorinostat y la poliquimioterapia.

Consenso peruano de diagnóstico y tratamiento de la micosis fungoides y síndrome de Sezary / A peruvian consensus for the diagnosis and therapy of mycosis fungoides and Sézary

Introducción: varias revisiones y guías de manejo de Micosis Fungoides (MF) y Síndrome Sézary (SS) han sido publicados. Sin embargo, estrategias terapeúticas para esta entidad varían entre instituciones y países. Existen pocos estudios fase III que permitan tomar decisiones en el tratamiento de MF/SS. Por tanto éste es frecuentemente determinado por las experiencias institucionales. Objetivo: con el objeto de sumarizar la evidencia disponible y revisar las mejores prácticas, es que se realizó un Consenso Peruano llevado a caboen Setiembre 2008 para establecer guías de diagnóstico y tratamientode MF/SS. Resultados: este artículo revisa los criterios clínicos, histopatológicos y terapéuticos de MF/SS.

Background: Several reviews and guidelines on the management of Mycosis Fungoides (MF) and Sézary syndrome (SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and among countries. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. Objetive: In order to summarise the available evidence and reviewbest practices, Peruvian Consensus met in September 2004 to establish guidelines for the diagnosis and treatment of MF/SS. Results: This article reviews hystopatologic, clinic and therapeutic criteria of MF/SS.

Síndrome de Sézary em cadela / Sézary syndrome in a bitch

The present report describes a case of Sezary syndrome in a canine with lymphadenomegaly, generalized erithroderma, intense pruritus and disseminated cutaneous nodules and plaques. Biopsy samples were taken from cutaneous nodules and plaques and were diagnosed epitheliotropic T cell cutaneous lymphoma by histology and immunohistochemical stain. Bone marrow cytology confirms leukemia. Diagnosis of Sezary syndrome was achieved through clinical, hematological, citopathological, histopathological and immunohistochemical findings. The patient was treated with Madison-Wisconsin chemotherapy protocol, but died after two mouths of treatment

A Case of Unspecified Mature T-cell Leukemia with Clover-shaped, Multi-lobated Nuclei

Mature T-cell leukemias are a group of neoplasms derived from mature or post-thymic T-cells, and a number of distinctive disease entities have been defined in the World Health Organization (WHO) classification. Here we report a 54-year-old female patient with multi-lobated atypical cells expressing the classic T-cell antigens involving multiple lymph nodes, peripheral blood, and bone marrow. The clinical, laboratory, and pathologic features of her disease did not fit into any of the entities in the WHO Classification. There was no evidence of rapidly rising lymphocyte counts, TCL1 expression, eosinophilia, erythroderma, Sezary cells, autoimmune phenomena, cytotoxic granules, nor evidence of HTLV-1 infection, and thus, T-cell prolymphocytic leukemia, Sezary syndrome, T-cell granular lymphocytic leukemia, and adult T-cell leukemia/lymphoma were all ruled out. This case suggests that further characterization and definition of the "unclassifiable" cases of mature T-cell neoplasm is needed to better understand the group of disorders.